Immunity Commons^™

Unraveling The Anti-Inflammatory Mechanisms And Efficacy Of Cannabidiol On The Progression Of A Murine Model Of Multiple Sclerosis From The Innate To The Adaptive Immune System To Clinical Symptoms, Christa Marie Frodella

Theses and Dissertations

Cannabidiol (CBD), a non-psychotropic phytocannabinoid with structural similarity to Δ 9 -tetrahydrocannabinol (THC), is currently being investigated as a therapeutic for its immunosuppressive effects. One disease for which CBD is extensively researched is multiple sclerosis (MS), a demyelinating, autoimmune disorder, and its murine model counterpart, experimental autoimmune encephalomyelitis (EAE). The focus of this dissertation aimed to analyze the transcriptomic brain pathways in EAE and its comparison to MS in addition to CBD’s immunosuppressive mechanisms in the innate and adaptive immune systems. Evidence presented here showed that transcriptomic signaling pathways in the EAE brain of mice with clinical symptoms were similar …

Characterization Of Innate Immune Responses In Mouse Trophoblast Stem Cells And Their Differentiated Cells, Mona Fendereski

Dissertations

The blastocyst is the preimplantation stage embryo consisting of two major components: the inner cell mass (ICM) and the trophectoderm (TE). The ICM forms the fetus, whereas the TE contributes to the placenta development. Previous studies have demonstrated that human and mouse embryonic stem cells (ESCs) derived from the ICM are deficient in expressing type I IFNs in response to viral infection. This study investigated the innate immune responses in mouse trophoblast stem cells (TSCs) and their in vitro differentiated trophoblasts (TSC-TBs). I report that, unlike ESCs, TSCs have a functional IFN system. They can express and respond to type …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat

Dissertations and Theses (Open Access)

Doxorubicin (Dox) is one of the most effective chemotherapy agents that is used for the treatment of childhood cancer. Unfortunately Dox treatment can cause damage to the heart. Indeed, childhood cancer survivors are at a higher risk of developing a cardiovascular disease at an earlier age. The mechanisms by which Dox causes acute and late cardiotoxicity are not completely understood. One understudied area in Dox-induced cardiotoxicity is the contribution of inflammation and innate immune cells, in particular neutrophils. Recognizing that neutrophils have been implicated in a number of heart diseases, we evaluated the role of neutrophils in Dox-induced cardiotoxicity. Here, …

Poliovirus Immunity Among Children Aged 6-11 And 36-48 Months In 14 Polio High-Risk Provinces Of Afghanistan: A Health-Facility-Based Study, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag, William S. Hendley, Derek Ehrhardt, Imran Ahmed, Imtiaz Hussain, William Weldon, Ahmed M. Kassem

Department of Paediatrics and Child Health

Afghanistan is one of two countries where wild poliovirus (WPV) type 1 remains endemic. We conducted a facility-based cross-sectional survey of antipoliovirus antibodies in children in 14 provinces of Afghanistan. The provinces were selected based on programmatic priorities for polio eradication. Children aged 6-11 and 36-48 months attending outpatient clinics were enrolled in the study. We collected venous blood, isolated serum, and conducted neutralization assays to detect poliovirus neutralizing antibodies. A total of 2086 children from the 14 provinces were enrolled. Among the enrolled children, 44.3% were girls; the median age in the 6-11-month group was 9.4 months, and in …

Elucidating The Mechanisms Underlying How Vmp1 Regulates Inflammatory Responses, Stephanie Zack

Dissertations

autophagy, inflammation, mitochondria, NLRP3 inflammasome, SERCA, VMP1

Elucidating The Mechanisms Of Immune Regulation By Bacillus Subtilis, Jesus Zamora-Pineda

Dissertations

bacillus subtilis, exopolysaccharides, inflammation, probiotics, tlr4

Effectiveness And Safety Of Immunosuppressants And Biological Therapy For Chronic Spontaneous Urticaria: A Network Meta-Analysis, Wen-Kuang Lin, Shwu-Jiuan Lin, Woan-Ruoh Lee, Chia-Chieh Lin, Weei-Chin Lin, Hua-Ching Chang, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect …

Function Of Atm And Msh2 During Dna Repair And Recombination, Emily Sible

Dissertations, Theses, and Capstone Projects

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm^-/- mice …

Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani

Electronic Theses and Dissertations

Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS …

Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez

Theses & Dissertations

Pancreatic cancer is currently the 3rd leading cause of all cancer-related deaths, with a 5-year survival rate remaining at 10%. The current standard treatment of care and a lack of effective diagnostic markers leaves patients with a dismal prognosis at advanced stages of the disease. This thesis research evaluated the effect of ApoE-expressing macrophages in the spleen. First, we aimed to assess the ApoE expression in the spleen of pancreatic tumor-bearing mice. Results showed that ApoE expression in splenic macrophages increased as the disease progressed. In addition, we saw a significant increase in marginal zone metallophilic macrophages and red pulp …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter

Dissertations

ABSTRACT

RNA interference (RNAi) is a pervasive gene regulatory mechanism in eukaryotes based on the action of multiple classes of small RNA (sRNA). Exploiting RNAi pathways in non-model systems have great potential for creating potent RNAi technologies. Here, we accessed RNAi-mediated control of gene expression in the two-spotted spider mite, Tetranychus urticae (T. urticae) using engineered dsRNA designed to modulate the host RNAi pathway and increase RNAi efficacy. Analysis of Dicer (Dcr) generated fragments revealed how exogenous RNAs access the host RNAi pathway in this animal, opening avenues for designing RNAi technology for their control. Further, some organisms …

Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud

Theses

Antimicrobial resistance (AMR) is a growing serious threat that poses a burden on the healthcare system. Spread of AMR bacteria limits treatment options; thus, new antimicrobial agents are required. Cefiderocol (CFDC) is a novel siderophore cephalosporin, approved by the FDA in 2019 for use in treating infections caused by multi-drug resistant (MDR) pathogens; but it is not yet in clinical use in the UAE. CFDC is equipped with stabilizers against β-lactamases as well as a siderophore side chain that allows it to penetrate the outer membrane of bacteria through the iron uptake pathways. The aim of this study is to …

Microbial Experience Increases Cytotoxicity Of Tumor-Infiltrating Cd8+ T Cells And Controls Tumor Growth, Nicholas Aaron Bunda

Masters Theses

Cancer immunotherapy research is traditionally conducted with specific pathogen-free (SPF) mice, which most accurately mimic the immune system of a human newborn. This makes translational research challenging, as this mouse model is not an accurate reflection of the adult patients who ultimately receive newly developed treatments. It is necessary to further develop a mouse model that bridges this gap and increases translatability of current cancer immunotherapy research.

By cohousing specific pathogen-free mice with regular pet store (PS) mice, we have generated a cohoused (CoH) mouse that reflects the microbial experience of an adult human immune system. We investigated antigen experience, …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Characterization Of Gangliosides And Fatty Acids In Extracellular Vesicles From Human Milk, Aliya Amin

Food Science (MS) Theses

Extracellular vesicles (EVs) are bioactive components of human milk that may impact functionality to regulate growth, cognitive development, metabolism, and immunity in newborns. The biogenesis of EVs and the mechanism by which EVs elicit biologic effects in vivo have not been characterized entirely. Gangliosides and fatty acids are integral in the formation, release, stability, and functionalities of EVs. Presumably, EV function is related to EV composition and lipids in EVs influence the bioavailability of EV cargo and downstream functions of EVs. The objective of this research was to characterize the fatty acid and ganglioside composition of EVs in human milk. …

Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos

Electronic Theses and Dissertations

Given the diversity and complexity within immunoglobulin (IG) loci, effective mouse models first require characterization of intra-strain differences and construction of high-quality reference assemblies for IG loci in several representative strains. To understand light chain germline diversity across biomedically significant mouse strains, we profiled the expressed IGK and IGL repertoires of 18 commonly used laboratory mouse strains using AIRR-seq. Across strains, we observed germline IGKV sequences shared by three different IGK haplotypes and a more conserved IGLV germline repertoire among common laboratory strains. Pacific Biosciences (PacBio) Single-Molecule Real-Time (SMRT) sequencing was used to sequence and assemble bacterial artificial chromosomes (BAC) …

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations and Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …

Aggregatibacter Actinomycetemcomitans Exploits And Modulates The Immune Response By Human Neutrophils For Survival In The Anaerobic Environment., Hazel Ozuna

Electronic Theses and Dissertations

Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative facultative anaerobe and an opportunistic oral pathogen, strongly associated with localized periodontitis and other inflammatory diseases. Periodontitis is a chronic inflammation of the periodontium resulting from the inflammatory response of the host towards the dysbiotic microbial community present at the gingival crevice. The host immune response creates a hostile environment for microorganisms; therefore, it is important for Aa to be able to regulate the necessary genes to survive and thrive in such an environment. Aaexpresses several virulence factors such as a cytolethal distending toxin (Cdt), lipopolysaccharide (LPS) and leukotoxin A (LtxA), …

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection. …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …

Increasing Human Papillomavirus Vaccination Intent And Knowledge Through An Educational Intervention, Angelica E. Musumeci

UNLV Theses, Dissertations, Professional Papers, and Capstones

Human papillomavirus (HPV) is a widely discussed topic in healthcare as it affects patients of all genders and ages who partake in sexual activity. The most significant concern it poses to those at risk is HPV-related cancer. Fortunately, a vaccination exists that targets specific strains associated with these types of cancers. Despite evidence-based research supporting the vaccination’s efficacy and safety, lack of awareness and misinformation diminish the receipt of the vaccine and drive the lack of protection. Thus, educational interventions directed at parents and caregivers, which aims to improve their understanding of HPV and the vaccination’s benefits, is key to …

Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel

Department of Paediatrics and Child Health

Despite the uncertainty about the follow up of COVID-19 survivors, there is a growing body of evidence supporting specific interventions including pulmonary rehabilitation, which may lead to a reduced hospital stay and improved overall respiratory function. The aim of this short report was to assess the attitudes toward pulmonary rehabilitation following COVID-19 among Ecuadorian physicians. A cross-sectional study was conducted, in which a 5-question survey was used to assess the level of agreement to specific statements with a 5-point Likert scale. Out of the 282 participants, 48.2% (n=136) were male, with a mean of 12.6 (SD=11.3) years of experience. More …

Salicylic Acid And N-Hydroxypipecolic Acid At The Fulcrum Of The Plant Immunity-Growth Equilibrium, Alyssa Shields, Vanessa Shivnauth, Christian Danve M. Castroverde

Biology Faculty Publications

Salicylic acid (SA) and N-hydroxypipecolic acid (NHP) are two central plant immune signals involved in both resistance at local sites of pathogen infection (basal resistance) and at distal uninfected sites after primary infection (systemic acquired resistance). Major discoveries and advances have led to deeper understanding of their biosynthesis and signaling during plant defense responses. In addition to their well-defined roles in immunity, recent research is emerging on their direct mechanistic impacts on plant growth and development. In this review, we will first provide an overview of how SA and NHP regulate local and systemic immune responses in plants. We …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian M. Gilbert, Jossie M. Santamaria, Gisela F. Erf

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Lipoteichoic acid (LTA) is a cell-wall polymer in Gram-positive bacteria that stimulates inflammation. Few studies have investigated in vivo immune response to LTA, and none of the in vivo studies have been performed in birds. For this project, the pulp (a skin derivative) of growing feathers (GF) of chickens was used to investigate the in vivo effects of intradermally injected LTA. In Study 1, GF of chickens were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 or 250 μg LTA/mL; 3 chickens/dose). Growing feathers were plucked before injection (0 h) and at 6, 24, 48, …

Response And Molecular Control Of Cd8 T Cells During Infection And Cancer, Nicholas K. Preiss Dr.

Dartmouth College Ph.D Dissertations

CD8 T cells are potent immune effector cells capable of vast clonal expansion and clearance of infected or cancerous cells. After control of the pathogenic insult, CD8 T cells develop into quiescent, long-lived memory populations that are poised to mediate rapid protection upon reencounter with cognate antigen. These properties make control of CD8 T cell responses a highly desirable outcome of vaccine strategies and immunotherapy. Therefore, understanding how the effector function and memory differentiation of CD8 T cells are controlled at a molecular level is of great importance. In the context of infection with gammaherpesviruses (γHV), which form a latent …

Social Determinants Of Disease: Hiv And Covid-19 Experiences, Raiza M. Beltran, Ian W. Holloway, Chenglin Hong, Ayako Miyashita, Luisita Cordero, Elizabeth Wu, Katherine Burris, Paula M. Frew

Epidemiology & Biostatistics Faculty Research

Purpose of Review: The differential impact of the COVID-19 and HIV pandemics on marginalized communities has renewed calls for more robust and deeper investigation into structural and social causes of health inequities contributing to these infections, including underlying factors related to systematic racism. Using the Social Determinants of Health (SDOH) framework, we analyzed parallel and divergent factors associated with COVID-19 and HIV/AIDS and the prevalence of disparate disease in diverse communities. We utilized PRISMA guidelines to identify relevant literature (N = 210 articles) that resulted in a review of 125 articles included in our synthesis. Recent Findings: With racial health …

Investigating The Interplay Of The Immune System, Skin Barrier, And Microbiome Following Dermal Exposure To Triclosan, Rachel Baur

Graduate Theses, Dissertations, and Problem Reports (ETD)

Triclosan is an antimicrobial chemical used in healthcare products that are applied to the skin. However, exposure to triclosan has been positively associated with food allergy, aeroallergy, and asthma severity in humans. In mice, dermal triclosan exposure, although not directly sensitizing, has been shown to augment the allergic response in a model of asthma. Furthermore, exposure to triclosan on mouse skin has been demonstrated to be immunomodulatory through the activity of thymic stromal lymphopoietin and S100 calcium-binding protein A8. The skin barrier and microbiome are known to interact with the immune system and disruptions in barrier integrity and the microbiome …

Tetramerization Of Stat5 Has Opposing Roles In Governing Autoimmune Pathogenesis, Kelly Lynn Monaghan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Signal transducers and activators of transcription 5 (STAT5A and STAT5B) are members of the STAT protein family. STAT5 plays a critical role in mediating cellular responses following cytokine stimulation. Critical STAT5 signaling is achieved following functional dimerization, which occurs via SH2 domain interactions. The binding of two STAT5 dimers to tandemly linked TTCN₃GAA γ-interferon-activated sequence (GAS) motifs and N-terminal domain interactions, facilitates functional tetramerization. The biological role of STAT5 tetramers has been investigated using the Stat5a-Stat5b N-domain double knock-in (DKI) mouse strain, in which STAT5 tetramers cannot be formed due to substitutions in critical amino acid …